The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid (original) (raw)

Abstract

Substantial evidence suggests that the accumulation of b-amyloid (Ab)-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well-de®ned plant extract containing two major groups of constituents, i.e.¯avonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Ab)-derived peptides (Ab 25±35 ,A b 1±40 and Ab 1±42 ) on hippocampal primary cultured cells, this area being severely affected in AD. A co-treatment with EGb 761 concentration-dependently (10±100 mg/ mL) protected hippocampal neurons against toxicity induced by Ab fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the¯avonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 mg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre-exposure to Ab 25±35 and Ab 1±40 . EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H 2 O 2 (50±150 mM), a major peroxide possibly involved in mediating Ab toxicity. Moreover, EGb 761 (10±100 mg/mL), and to a lesser extent CP 205 (10±50 mg/mL), completely blocked Ab-induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Ab-induced toxicity and cell death.

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